1. Field of the Invention
The present invention relates generally to a eutectic-based self-nanoemulsified drug delivery system (herein referred to as “SNEDDS”). The eutectic-based SNEDDS is preferably used to administer poorly water soluble drugs to a patient.
2. Description of Related Art
Large proportions of new drug candidates have poor water solubility. To overcome these problems, various formulation strategies were reported, including complexation with cyclodextrin, solid dispersions and co-precipitates. In recent years, however, much attention has been focused on lipid based formulations, with particular emphasis on self-emulsifying drug delivery systems (herein referred to as “SEDDS”). SEDDS are isotropic mixtures of oil, surfactant, co-surfactant and drug that form fine oil-in-water emulsion when introduced into aqueous medium under gentle agitation.
Ubiquinone, also known as Coenzyme Q10 (herein referred to as “CoQ10”), is an important component of the mitochondrial respiratory chain. The structure of CoQ10 is as follows:
Because of its poor water solubility, CoQ10 presents a challenge when developing a formulation for oral administration. Many approaches have been used to improve the in vitro dissolution of CoQ10. Some of the approaches include complexation with cyclodextrins, solubilization in a blend of polysorbate 80 and medium chain triglycerides, preparation of redispersible dry emulsion, solid dispersion, and recently, development of a self-emulsified drug delivery system (SEDDS).
In the traditional methods of preparing self-emulsified delivery systems, active ingredients are dissolved in fixed oils or triglycerides and subsequently blended with suitable solubilizing agents. However, due to limited solubility of some drugs, such as CoQ10, in these oils, such methods often result in low drug loading and suffer from irreversible precipitation of the active ingredient and/or the excipient with time.
Emulsion systems based on a eutectic mixture of lidocaine-prilocaine and lidocaine-menthol were used in preparation of topical formulations. However, little is known about the use of eutectic mixtures for the preparation of self-emulsified formulation.
Formulations containing SEDDS also require filling into soft or hard gelatin capsules. Therefore, the incorporation of self-emulsifying vehicles into a powder to produce solid dosage forms would be of great interest. Recently, pellets containing a self-emulsifying mixture were prepared by extrusion-spheronization. Solid-state microemulsion for the delivery of cyclosporin also was prepared by coating the premicroemulsion with an enteric material. Similarly, a solvent-evaporation method was used to prepare tocopheryl nicotinate tablets using calcium silicates as the adsorbing agent. Such methods often require elaborate processing and instrumentation.
On the other hand, solid solutions and liquisolids were produced by blending liquid medications with selected powder excipients to produce free-flowing, readily compressible powders. Such excipients include cellulose or lactose as the carriers and fine silicates as the coating material. Using a similar approach, a solid dosage form based on microemulsion adsorbed onto colloidal silicon dioxide and microcrystalline cellulose was introduced. In most cases as well as in the case of liquisolids, however, adsorbed oil- or lipid-based formulations form a thin film of oil on the surface of the powder. This film causes particles to adhere and produces a mass that exhibits poor flow and tableting characteristics. To improve flow and compaction properties, oil loading is reduced, or fine particulates such as silicates are added in quantities often exceeding the limits stated by the Code of Federal Regulations.